We propose to undertake a novel study of individuals who receive occupational exposure to high levels of noise for identification of gene mutations that result in predisposition to noise-induced hearing loss (NIHL). Military personnel who are exposed to high levels of noise during training exercises will be subjected to pre-and post-exposure audiometric evaluations to document changes in hearing thresholds. Preliminary information indicates that about 10-15 percent of these Marine personnel will develop permanent shifts in hearing threshold (PTS). Blood samples will be obtained from PTS subjects and unaffected subjects and then screened for mutations associated with non-syndromic deafness and hearing impairment gene mutations. The subjects will be surveyed by questionnaire to determine if the frequency of hearing impairment among first and second degree relatives or other factors are predictive of NIHL sensitivity. Subjects with NIHL may exhibit an increased frequency of one or more inherited gene mutations; perhaps as the result of being carriers for a recessively inherited non-syndromic deafness trait (congenital), a dominantly inherited later age of onset hearing impairment gene or one of several mitochondrial DNA mutations. In future studies, we plan to investigate if mutations in gene products that are important in the recovery from acoustic trauma or chronic auditory overstimulation are genetic determinants of NIHL sensitivity. These candidates include enzymes and other cellular components that are part of the oxidative phosphorylation pathway or that are involved in the neutralization of reactive oxygen species produced by the overstimulation of the auditory system. This application is a new collaboration among investigators who have experience in the areas that are critical for its success including: molecular genetics, experimental auditory physiology and clinical aspects of noise induced hearing loss. These studies represent an important new approach toward investigation of molecular genetic factors in NIHL.